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15 pages, 2711 KiB

Open AccessArticle

Proposed Refinement of 2022 European LeukemiaNet Adverse-Risk Group of AML Patients Using a Real-World Cohort

by Collins Wangulu, Davidson Zhao, Qianghua Zhou, Cuihong Wei, Rajat Kumar, Aaron Schimmer and Hong Chang

Cancers 2025, 17(9), 1405; https://doi.org/10.3390/cancers17091405 - 23 Apr 2025

Abstract

Background/Objectives: The 2022 European LeukemiaNet (ELN 2022) is a widely used genotypic risk classification tool for the treatment and prognostication of acute myeloid leukemia (AML) patients. Our study evaluates its effectiveness in categorizing adverse-risk AML patients on standard therapy based on their overall [...] Read more.

Background/Objectives: The 2022 European LeukemiaNet (ELN 2022) is a widely used genotypic risk classification tool for the treatment and prognostication of acute myeloid leukemia (AML) patients. Our study evaluates its effectiveness in categorizing adverse-risk AML patients on standard therapy based on their overall survival (OS). Methods: We conducted a retrospective study involving 256 AML patients. Results: Those in the ELN 2022 adverse-risk group had the shortest OS (p < 0.0001) and were predominantly characterized by myelodysplasia-related (MR) mutations, complex karyotype (CK), monosomal karyotype (MK), and TP53 mutation (TP53 Mut). Subclassification and analysis of this adverse-risk group based on the TP53 Mut status revealed a significantly shorter OS compared to the adverse TP53 wild-type (TP53 WT) counterparts (p = 0.0036). We propose refining the ELN 2022 adverse-risk group into two categories, adverse TP53 Mut and adverse TP53 WT groups, to represent adverse- and ultra-adverse-risk groups, respectively. We used an external validation dataset to confirm our findings. Conclusions: This refinement allows for a more accurate classification of these adverse-risk patients based on their clinical outcomes. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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18 pages, 2412 KiB

Open AccessArticle

MicroRNAs in Diffuse Large B-Cell Lymphoma (DLBCL): Biomarkers with Prognostic Potential

by Yuliya A. Veryaskina, Sergei E. Titov, Igor B. Kovynev, Sofya S. Fyodorova, Olga V. Berezina, Igor P. Zhurakovskij, Oksana V. Antonenko, Sergei A. Demakov, Pavel S. Demenkov, Pavel S. Ruzankin, Anton S. Tarasenko, Tatiana I. Pospelova and Igor F. Zhimulev

Cancers 2025, 17(), 1300; https://doi.org/10.3390/cancers17081300 - 12 Apr 2025

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Abstract

Background/Objectives: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) based on differences in both genetic and epigenetic factors contributes to the dynamics of tumor growth and efficacy of cytoreductive therapy, as well as considerably affecting disease prognosis. This study aimed to detect [...] Read more.

Background/Objectives: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) based on differences in both genetic and epigenetic factors contributes to the dynamics of tumor growth and efficacy of cytoreductive therapy, as well as considerably affecting disease prognosis. This study aimed to detect microRNAs (miRNAs) capable of improving prognostic accuracy in DLBCL patients. Methods: We performed miRNA sequencing in bone marrow (BM) samples collected from DLBCL patients. Next, the expression levels of miRNAs in lymph node (LN) samples (n = 43) and BM samples (n = 70) were analyzed by real-time RT-PCR in the group of DLBCL patients. Results: It was found that the expression levels of miRNA-10b, -100, -125a, -125b, -126, -143, -23a and let-7a were statistically significantly reduced in the group of DLBCL patients who had a poor prognosis compared to DLBCL patients with a favorable prognosis (p < 0.05). Kaplan–Meier survival analysis demonstrated that the upregulated expression of miRNA-23a, miRNA-125a, and miRNA-100 was associated with better overall survival in DLBCL patients. A statistically significant elevation in the expression levels of miRNA-151a, miRNA-148b and miRNA-192 in the BM samples was observed for DLBCL patients both with and without BM involvement compared to BM samples from non-cancerous blood disease (NCBD) patients (p < 0.05). Statistically significant upregulation of PD-L1, TIMP1, TOP2A, and TP53 was observed in BM samples from DLBCL patients with and without BM involvement in comparison with BM samples from NCBD patients (p < 0.05). Conclusions: miRNA-23a, miRNA-125a, and miRNA-100 were shown to be potential prognostically significant biomarkers in DLBCL patients. Changes in expression levels of miRNA-151a, miRNA-148b, miRNA-192, PD-L1, TIMP1, TOP2A, and TP53 reflect alterations in the BM without morphological or immunophenotypic signs of a DLBCL-related BM pathology. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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15 pages, 3612 KiB

Open AccessArticle

Novel Recurrent Cytogenetic Abnormalities Predict Overall Survival in Tetraploid/Near-Tetraploid Myelodysplastic Syndrome and Acute Myeloid Leukemia

by Matthew R. Avenarius, Zachary B. Abrams, Ling Guo, James S. Blachly, Cecelia R. Miller, Nyla A. Heerema, Guilin Tang, Kevin R. Coombes and Lynne V. Abruzzo

Cancers 2025, 17(), 1277; https://doi.org/10.3390/cancers17081277 - 10 Apr 2025

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Abstract

Background/Objectives: Tetraploidy (4n = 92 chromosomes) and near-tetraploidy (81–103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML (~1%). Abnormalities reported to be associated with T/NT MDS/AML include −5/del(5q), −7/del(7q), +8, and +21. However, other clinically relevant abnormalities likely remain “hidden” in long strings [...] Read more.

Background/Objectives: Tetraploidy (4n = 92 chromosomes) and near-tetraploidy (81–103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML (~1%). Abnormalities reported to be associated with T/NT MDS/AML include −5/del(5q), −7/del(7q), +8, and +21. However, other clinically relevant abnormalities likely remain “hidden” in long strings of ISCN cytogenetic nomenclature when evaluated visually. To date, no studies have had the statistical power and a computational method to identify novel recurrent abnormalities associated with the T/NT karyotype or overall survival (OS). Methods: Using CytoGPS, a bioinformatic tool we developed, we converted karyotypes from a combined cohort of 75 T/NT MDS/AML cases from two institutions into a binary Loss–Gain–Fusion model, which is analyzable using computational methods. Results: On univariate analyses, age as a continuous variable (p = 0.032), prior treatment (p = 0.011), and cohort (p = 0.025) were associated with OS; age ≥ 60 years (p = 0.316), gender (p = 0.916), karyotypic complexity (p = 0.175), time from diagnosis to T/NT karyotype identification (p = 0.419), and clone size (p = 0.316) had no effect. Univariate analyses of karyotypes demonstrated that −5, −16, −18, del(11)(p15.1p15.4), del(13)(q12.11q22.3), and +8 were associated with poorer OS (unadjusted p < 0.05). Conclusions: Using the results of univariate analyses to build multivariate models of OS, the best predictor of OS was the presence of any one of these six cytogenetic abnormalities. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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20 pages, 3523 KiB

Open AccessArticle

Characterization of a 3S PRAME VLD-Specific T Cell Receptor and Its Use in Investigational Medicinal Products for TCR-T Therapy of Patients with Myeloid Malignancies

by Maja Bürdek, Petra U. Prinz, Kathrin Mutze, Stefanie Tippmer, Christiane Geiger, Giulia Longinotti and Dolores J. Schendel

Cancers 2025, 17(2), 242; https://doi.org/10.3390/cancers17020242 - 13 Jan 2025

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Abstract

Background/Objectives: MDG1011 is an autologous TCR-T therapy developed as a treatment option for patients with myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). It is specific for the target antigen PReferentially expressed Antigen in MElanoma (PRAME). The [...] Read more.

Background/Objectives: MDG1011 is an autologous TCR-T therapy developed as a treatment option for patients with myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). It is specific for the target antigen PReferentially expressed Antigen in MElanoma (PRAME). The recombinant TCR used in MDG1011 recognizes PRAME_100–108 VLD-peptide presented by HLA-A*02:01-encoded surface molecules. Methods: Two preclinical batches of MDG1011, produced from enriched CD8+ T cells of healthy donors, underwent rigorous evaluation of on-target and off-target recognition of tumor cells and test cells representing healthy tissues. MDG1011 investigational medicinal products (IMPs) were produced for 13 patients. VLD-TCR surface expression was assessed using dual-marker flow cytometry using TCR V-beta-specific antibody and VLD/HLA-A2-specific multimer. Functionality was assessed by interferon-gamma (IFN-γ) secretion and cell-mediated cytotoxicity of target cells. Results: Preclinical MDG1011 batches displayed strong VLD-TCR expression, cytokine secretion, and cytotoxicity after antigen-specific activation, while showing no signals of on-target/off-tumor or off-target recognition. All IMPs had good VLD-TCR expression as well as functionality after activation by multiple target cells. Conclusions: Preclinical studies demonstrated that MDG1011 displayed key 3S attributes of high specificity, sensitivity, and safety required for regulatory approval of a first-in-human (FIH) clinical study of patients with myeloid malignancies (CD-TCR-001: ClinicalTrials.gov Identifier: NCT03503968). MDG1011 IMP manufacturing was successful at 92%, even including heavily pretreated elderly patients with very advanced disease. The IMPs applied in nine patients all displayed antigen-specific functionality. Elsewhere, clinical study results for MDG1011 showed no dose-limiting toxicity and signs of biological and/or clinical activity in several patients. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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14 pages, 568 KiB

Open AccessArticle

Using Deauville Scoring to Guide Consolidative Radiotherapy in Diffuse Large B-Cell Lymphoma

by Chun En Yau, Chen Ee Low, Whee Sze Ong, Lay Poh Khoo, Joshua Tian Ming Hoe, Ya Hwee Tan, Esther Wei Yin Chang, Valerie Shiwen Yang, Eileen Yi Ling Poon, Jason Yongsheng Chan, Iris Huili Sin, Kheng Wei Yeoh, Nagavalli Somasundaram, Mohamed Farid Bin Harunal Rashid, Miriam Tao, Soon Thye Lim and Jianbang Chiang

Cancers 2024, 16(19), 3311; https://doi.org/10.3390/cancers16193311 - 27 Sep 2024

Viewed by 1049

Abstract

Background: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, [...] Read more.

Background: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), to guide the utilization of consolidative RT, which may help spare low-risk DLBCL patients from unnecessary RT. Methods: We included all DLBCL patients diagnosed between 2010 and 2022 at the National Cancer Centre Singapore with DV measured at the end of the first-line chemoimmunotherapy. The outcome measure was time-to-progression (TTP). The predictive value of DV for RT was assessed based on the interaction effect between the receipt of RT and DV in Cox regression models. Results: The data of 349 patients were analyzed. The median follow-up time was 38.1 months (interquartile range 34.0–42.3 months). RT was associated with a significant improvement in TTP amongst the DV4-5 patients (HR 0.33; 95%CI 0.13–0.88; p = 0.027) but not the DV1-3 patients (HR 0.85; 95%CI 0.40–1.81; p = 0.671) (interaction’s p = 0.133). Multivariable analysis reported that RT was again significantly associated with improved TTP among the DV4-5 patients (adjusted HR 0.29; 95%CI 0.10–0.80; p = 0.017) but not the DV1-3 group (HR 0.86; 95%CI 0.40–1.86; p = 0.707) (interaction’s p = 0.087). Conclusion: Our results suggests that DLBCL patients with end-of-treatment PET-CT DV1-3 may not need consolidative RT. Longer follow-up and prospective randomized trials are still necessary to investigate long-term outcomes. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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12 pages, 1451 KiB

Open AccessArticle

Erdheim–Chester Disease: Investigating the Correlation between Targeted Treatment Therapy and Disease Outcomes

by Sabrina R. Wilcox, Samuel B. Reynolds and Asra Z. Ahmed

Cancers 2024, 16(7), 1299; https://doi.org/10.3390/cancers16071299 - 27 Mar 2024

Viewed by 1296

Abstract

A retrospective analysis of 20 adult patients with histopathological and clinical diagnoses of ECD was conducted at a single institution over a twenty-year period (2002–2022). Clinical responses were compared on the basis of treatments rendered, which included chemotherapy, immunotherapy, systemic corticosteroids, surgery and [...] Read more.

A retrospective analysis of 20 adult patients with histopathological and clinical diagnoses of ECD was conducted at a single institution over a twenty-year period (2002–2022). Clinical responses were compared on the basis of treatments rendered, which included chemotherapy, immunotherapy, systemic corticosteroids, surgery and radiation, or targeted agents, referring to any small molecular inhibitors. Treatment response evaluation varied by the anatomic site(s) of disease, the extent of disease at diagnosis, and the imaging modality employed. In this analysis, patients were treated with a combination of targeted agents, myelosuppressive therapies, and radiation at various points in their disease courses. Of these, the most common treatment modality rendered was targeted therapy, employed in 11 of 20 patients. Partial responses or better were observed in 15 of 20 patients. Rates of stable disease trended towards being more frequent with targeted therapy versus conventional therapy but did not reach significance (p = 0.2967). Complete response rates trended towards being more common with conventional therapy than molecular (p = 0.5) but were equivocal overall. Trends of peripheral blood absolute monocytes with relation to disease activity were reviewed as recent literature implied that monocyte levels surrounding disease progression were of potential prognostic significance in histiocytic diseases. Amongst the patients who progressed at any point during their treatment course, absolute monocyte count (in K/µL) was identified at the closest available timepoint prior to or following disease progression and at the lowest value (nadir) following re-institution of therapy prior to any additional agent(s) being employed. There was no statistically significant difference in either of these monocyte values nor in disease outcomes with respect to treatments rendered within our cohort. However, our cohort consists of a heterogenous population of patients with ECD with data that highlights several trends over a longitudinal period, spanning the advent of targeted therapy. Significant differences are anticipated in ongoing analyses. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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17 pages, 2487 KiB

Open AccessArticle

Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis

by Nicole Naumann, Martina Rudelius, Johannes Lübke, Deborah Christen, Jakob Bresser, Karl Sotlar, Georgia Metzgeroth, Alice Fabarius, Wolf-Karsten Hofmann, Jens Panse, Hans-Peter Horny, Nicholas C. P. Cross, Andreas Reiter and Juliana Schwaab

Cancers 2024, 16(3), 593; https://doi.org/10.3390/cancers16030593 - 30 Jan 2024

Cited by 2 | Viewed by 1734

Abstract

Within our nationwide registry, we identified a KIT D816V mutation (KIT D816V^pos.) in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the [...] Read more.

Within our nationwide registry, we identified a KIT D816V mutation (KIT D816V^pos.) in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics of KIT D816V-negative (D816V^neg.) AdvSM. In 19 D816V^neg. patients, a combination of clinical, morphological and genetic features revealed three subgroups: (a) KIT D816H- or Y-positive SM (KIT D816H/Y^pos., n = 7), predominantly presenting as mast cell leukemia (MCL; 6/7 patients), (b) MCL with negative KIT sequencing (KIT^neg. MCL, n = 7) and (c) KIT^neg. SM with associated hematologic neoplasm (KIT^neg. SM-AHN, n = 5). Although >70% of patients in the two MCL cohorts (KIT D816H/Y^pos. and KIT^neg.) were classified as low/intermediate risk according to prognostic scoring systems (PSS), treatment response was poor and median OS was shorter than in a KIT D816V^pos. MCL control cohort (n = 29; 1.7 vs. 0.9 vs. 2.6 years; p < 0.04). The KIT^neg. SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816V^neg. patients. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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10 pages, 2247 KiB

Open AccessArticle

CD30 Lateral Flow and Enzyme-Linked Immunosorbent Assays for Detection of BIA-ALCL: A Pilot Study

by Victoria G. Zeyl, Haiying Xu, Imran Khan, Jason T. Machan, Mark W. Clemens, Honghua Hu, Anand Deva, Caroline Glicksman, Patricia McGuire, William P. Adams, Jr., David Sieber, Mithun Sinha and Marshall E. Kadin

Cancers 2023, 15(21), 5128; https://doi.org/10.3390/cancers15215128 - 25 Oct 2023

Cited by 1 | Viewed by 2855

Abstract

Introduction: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection [...] Read more.

Introduction: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists’ interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. Methods: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. Results: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250–500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. Conclusions: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (<20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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12 pages, 1860 KiB

Open AccessArticle

Survival of Patients with Acute Coronary Syndrome and Hematologic Malignancies—A Real-World Analysis

by Stefan A. Lange, Christoph Schliemann, Christiane Engelbertz, Jannik Feld, Lena Makowski, Joachim Gerß, Patrik Dröge, Thomas Ruhnke, Christian Günster, Holger Reinecke and Jeanette Köppe

Cancers 2023, 15(20), 4966; https://doi.org/10.3390/cancers15204966 - 12 Oct 2023

Cited by 2 | Viewed by 1705

Abstract

Background: The impact of the encounter between coronary heart disease (CHD) and cancer, and in particular hematologic malignancies (HM), remains poorly understood. Objective: The aim of this analysis was to clarify how HM affects the prognosis of acute coronary syndrome (ACS). We analyzed [...] Read more.

Background: The impact of the encounter between coronary heart disease (CHD) and cancer, and in particular hematologic malignancies (HM), remains poorly understood. Objective: The aim of this analysis was to clarify how HM affects the prognosis of acute coronary syndrome (ACS). We analyzed German health insurance data from 11 regional Ortskrankenkassen (AOK) of patients hospitalized for ACS between January 2010 and December 2018, matched by age, sex and all comorbidities for short- and long-term survival and major adverse cardiac events (MACE). Results: Of 439,716 patients with ACS, 2104 (0.5%) also had an HM. Myelodysplastic/myeloproliferative disorders (27.7%), lymphocytic leukemias (24.8%), and multiple myeloma (22.4%) predominated. These patients were about 6 years older (78 vs. 72 years *). They had an ST-segment elevation myocardial infarction (STEMI, 18.2 vs. 34.9% *) less often and more often had a non-STEMI (NSTEMI, 81.8 vs. 65.1% *). With the exception of dyslipidemia, these patients had more concomitant and previous cardiovascular disease and a worse NYHA stage. They were less likely to undergo coronary angiography (65.3 vs. 71.6% *) and percutaneous coronary intervention (PCI, 44.3 vs. 52.0% *), although the number of bleeding events was not relevantly increased (p = 0.22). After adjustment for the patients’ risk profile, the HM was associated with reduced long-term survival. However, this was not true for short-term survival. Here, there was no difference in the STEMI patients, * p < 0.001. Conclusion: Survival in ACS and HM is significantly lower, possibly due to the avoidance of PCI because of a perceived increased risk of bleeding. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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12 pages, 970 KiB

Open AccessArticle

Prognostic Significance of the Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) in Patients with Myelofibrosis: A Retrospective Study

by Kira-Lee Koster, Nora-Medea Messerich, Thomas Volken, Sergio Cogliatti, Thomas Lehmann, Lukas Graf, Andreas Holbro, Rudolf Benz, Izadora Demmer, Wolfram Jochum, Tata Nageswara Rao and Tobias Silzle

Cancers 2023, 15(19), 4698; https://doi.org/10.3390/cancers15194698 - 24 Sep 2023

Cited by 1 | Viewed by 2152

Abstract

In myelofibrosis, comorbidities (CMs) add prognostic information independently from the Dynamic International Prognostic Scoring System (DIPSS). The Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) offers a simple tool for CM assessment as it is calculable after having performed a careful history and physical examination, a [...] Read more.

In myelofibrosis, comorbidities (CMs) add prognostic information independently from the Dynamic International Prognostic Scoring System (DIPSS). The Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) offers a simple tool for CM assessment as it is calculable after having performed a careful history and physical examination, a small routine chemistry panel (including creatinine and liver enzymes) and a limited set of functional diagnostics. To assess the prognostic impact of the MDS-CI in addition to the DIPSS and the Mutation-Enhanced International Prognostic Scoring System (MIPSS)-70, we performed a retrospective chart review of 70 MF patients who had not received allogeneic stem cell transplantation (primary MF, n = 51; secondary MF, n = 19; median follow-up, 40 months) diagnosed at our institution between 2000 and 2020. Cardiac diseases (23/70) and solid tumors (12/70) were the most common CMs observed at MF diagnosis. Overall survival (OS) was significantly influenced by the MDS-CI (median OS MDS-CI low (n = 38): 101 months; MDS-CI intermediate (n = 25): 50 months; and high (n = 7): 8 months; p < 0.001). The MDS-CI added prognostic information after inclusion as a categorical variable in a multivariate model together with the dichotomized DIPSS or the dichotomized MIPSS70: MDS-CI high HR 14.64 (95% CI 4.42; 48.48), p = 0.0002, and MDS-CI intermediate HR 1.97 (95% CI 0.96; 4.03), p = 0.065, and MDS-CI high HR 19.65 (95% CI 4.71; 81.95), p < 0.001, and MDS-CI intermediate HR 1.063 (95% CI 0.65; 4.06), p = 0.2961, respectively. The analysis of our small and retrospective MF cohort suggests that the MDS-CI represents a useful tool to identify MF patients with an increased vulnerability due to comorbidities. However, analyses of larger cohorts are necessary to define the value of the MDS-CI as a prognostic tool in comparison with other comorbidity indices. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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Review

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13 pages, 234 KiB

Open AccessReview

Revisiting the Role of Day 14 Bone Marrow Biopsy in Acute Myeloid Leukemia

by Omer Jamy, Garrett Bourne, Todd William Mudd, Haley Thigpen and Ravi Bhatia

Cancers 2025, 17(5), 900; https://doi.org/10.3390/cancers17050900 - 6 Mar 2025

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Abstract

In recent years, the practice of routinely obtaining day 14 bone marrow biopsies during AML intensive induction therapy has been scrutinized. While current guidelines recommend obtaining mid-induction biopsies to gauge early response to treatment and guide potential changes in future management, concerns have [...] Read more.

In recent years, the practice of routinely obtaining day 14 bone marrow biopsies during AML intensive induction therapy has been scrutinized. While current guidelines recommend obtaining mid-induction biopsies to gauge early response to treatment and guide potential changes in future management, concerns have been raised that these biopsies may not be as prognostically accurate as hoped and subsequently may result in additional and unwarranted chemotherapy toxicity in select patients. In this review, our goal is to summarize the most recent evidence surrounding day 14 bone marrow biopsies that have been published and clarify the utility of this currently recommended practice. Here, we review major developments in mid-induction biopsy in AML, along with ongoing and future planned studies in this area, outlining the limitations of available data and our future goals. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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